Substituted halo-phenol carboxylic acids and their salts



Patented June 10, 1 941 UNITED STATES PATENT OFFICE- SUBSTITUTEDHALO-PHENOL OARBOXYLIO ACIDS AND THEIR SALTS George L. Doelling, St.Louis, M0. N Drawing. Application August 27, 1938.

Serial No. 227,065

8 Claims. (Cl. 260-521) This invention relates to compoundscomprisjects. These compounds may be described by ing substitutedhalo-phenol carboxylic acids and the following formula: especially theirsalts which are particularly use- OH 0002 ful as antiseptics.

Many of the present types of antiseptics and 5 aur 1: disinfectantsubstances such as cresols, xylenols, (Y) amyl cresols, chlorthymol, andothers are very in which may be a benzene nucleus, X poorly soluble inwater. Some of these are sola halogen and Y an alkyl, .amlkyl, aryl,alkoxy, uble t0 the extent of only a; few thousandths or cycloalkylgroup of there may .be one of Q Per cent in water at room temperature-10 two, or three for each molecule, the number of Whlle it is true thatsome solvent other than these substituent groups present per mgleculewater may be used, 1S the antisepbeing given by 71 These alkyl groupsneed not tic will be precipitated out of solution when its be the Same tthere may be t or more djfsolvent is diluted by blood serum otherfiuidsferent substituent groups in the same molecule. Since mostbacteria, live in an aqueous medium, Z inthe above formula may be ahydrogen or an antiseptic should have a fair degree of 0 a,nitrogen-containing basic radical or a metal bihty in water m OrderTeach the organismsnot lower than zinc in the electromotive series Itis, therefore, an object of this invention to and n an integer notgreater than t The provide an antiseptic having the proper solubilityalkyl, aralkyl aryl, alkoxy and cycloalkyl ha,] o m Water- 29phenol-carboxylic acids and especially their salts It is anOthGr Objectof this invention o PIO- have been found to be especially Valuable as anantiseptic which does not have bad antiseptics and disinfectants. Thepreferred Odor P acteristictof some 9 P Present typescompounds in thisclass are those in which the It 15 also an 01339 of thls mvefltionsubstituent alkyl, aralkyl, aryl, alkoxy, or cyclovide an antisepticwhich is not either strongly alkyl group or groups have a total f notless acidic or alkaline but! is a Substantially neutral than three normore twelve carbon atoms substance. Many of the chlorine compounds perm01ecu1e such as NaOCl, chloramine T, and others are I not always stablein solution and often deteriorate on the shelf so that there is alwaysthe carboxylic acid of pwmorothymol having the danger of someone using asolution which has following formula; lost most of its free chlorinecontent and hence has no antiseptic value. A good antiseptic OH should,therefore, be a stable substance in solution and it is an object of thisinvention to pro- CH- 00011 vide an antiseptic fulfilling thisrequirement. CH

Other antiseptics such as hydrogen peroxide OH; and iodine are vigorousoxidizing agents and their effectiveness is often wasted in oxidizinghealthy 01 tissues. It is, therefore, another object of this I inventionto provide an antiseptic which is not was made by reacung 60 grams of clorthv ol, too igorous an oxidizing agent. 11.7 grams of NaOH, and 40 c.c. of water to F r th purpose of illu trati I will n w 1 form a sodiumsalt. Some xylene was then added scribe several examples of antisepticswhich I to the sodium salt in a distilling flask and water have found tofulfill the above objects as well completely removed by distillation.After all the as methods of producing some of them, although Water wasremoved, about 200 c. c. of orthoit is to be understood that suchdisclosure is to dichlorbenzene was added and at 110 to 1 be regarded asillustrative and not limitative. Carbon diOXide was led in with theSystem I have found that certain of the substituted un r a pr su f about40 inches of water halo-phenol carboxylic acids and especially theirover a period of about six hours. The product salts provide antisepticsfulfilling the above obwas recovered by the usual methods. It had amelting point of 161 to 162 C., and had the calculated neutralizationvalue of chlorthymol carboxylic acid. A neutral solution of the sodiumsalt gave a bluish violet color with ferric chloride. Bacteriologicaltests of this compound in water solution showed that a solution of .75gram of the acid in 100 c. c. of solution (present as sodium salt)killed both B. typhosus and Staphylococcus aureus in fifteen minutes.The ethylene diamine salt of this chlorthymol carboxylic acid was madeby neutralizing the acid with ethylene diamine. A solution containing .3gram of this acid in 100 c. c. of solution (present as the ethylenediamine salt) killed both of the above mentioned organisms in fifteenminutes. Instead of p-chlorothymol, chlor carvacrol can be used.

Chloro-para-tertiary-amyl-phenol-ortho-carboxylic acid having thefollowing formula:

01- COOH was made by chlorinating p-tertiary amyl phenol and thentreating the chlor-p-tert-amyl-phenol with sodium hydroxide and CO2 asin the above example. Thisortho-chlor-para-tertiary-amylphenol-ortho-carboxylic acid had a meltingpoint of 141.5 to 143 C., had the correct neutralization equivalent, andthe neutral solution of its sodium salt gave a strong purplish violetcolor with ferric chloride. The sodium salt of this acid was made andtested in water solution against B. typhosus and Staphylococcus aureus.A solution containing .75 gram of the acid (present as its salt) per 100c. c. of solution killed both these organisms in ten minutes. Theethylene diamine salt was made by neutralizing the acid with ethylenediamine. A solution containing about .55 gram of the acid (present assalt) in 100 c. 0. killed both organisms in ten minutes.

Obviously, isomeric substances can be used, as for example, secondaryamyl in place of tertiary amyl, etc. Likewise, bromine or iodine can besubstituted for the chlorine, and benzyl, amoxy, cyclohexyl, or otherradicals of similar nature can be substituted for the tertiary amyl andmethyl-isopropyl given above. In the basic radical, calcium, magnesium,Zinc, potassium, ammonium, butylamine, amylamine, alkylene diamines suchas ethylenediamine or propylene diamine, and other basic substances canbe used. In general though, the metals below zinc in the electromotiveseries are not suitable.

The compounds just described have antiseptic properties which recommendtheir use in various fields. Thus they may be used as disinfectants inplace of cresylic acid or similar compounds, while at the same time,they may be used with advantage in lotions, antiseptic solutions,ointments, hair tonics, salves, creams, etc. These compounds may be usedin a water solution, in dry form, or with a solvent such as alcohol orpropanol. The particular form in which they are used will be determinedby the nature of their use. They have been found particularly useful forkilling or inhibiting the growth of bacteria,

bacilli, and other micro-organisms either in contact with living tissuesor as a general disinfectant. Because of the nature of the antisepticsthus provided, that is, their freedom from odor, stableness in solution,freedom from staining, water solubility, etc., many uses in addition tothose enumerated will become apparent.

While I have described in some detail the preferred embodiments of myinvention and some variations thereof, it will be understood that thisis only for the purpose of making the invention clearer and it is not tobe regarded as limited to the details described but is to be regarded aslimited only by the terms of the accompanying claims in which it is myintention to claim all novelty inherent therein as broadly as ispossible in view of the prior art.

I claim:

1. A chemical compound comprising a salt in which the acid radical is asubstituted halophenol carbcxylic acid containing at least one but notmore than three substituent groups each of. which is one of the groupwhich consists of the alkyl, aralkyl, aryl, alkoxy and cycloalkylgroups, the total number of carbon atoms in the substituent groups beingnot less than three nor more than twelve per molecule, and in which thebasic radical is one of the group consisting of hydrogen, analkali-metal, an alkaline-earth-metal, ammonium, and a lower aliphaticamine.

2. As a new compound:

0H CH3 l on o 0 on CH3 3. A. compound having the formula OH CH3\ 1 011--o 0 oz in whichZ is a member of the class consisting of hydrogen, analkali-metal, an alkaline-earthmetal, ammonium, and a lower aliphaticamine.

4:. As an antiseptic an alkyl-substituted halosalicylic acid in whichthe total number of carbon atoms in the alkyl group or groups is notless than three nor more than twelve per molecule.

5. A compound selected from the group consisting of an alkyl-substitutedhalo-salicylic acid, the total number of carbon atoms in the alkyl groupor groups being not less than three nor more than twelve per molecule,and salts of the said acid.

6. As a new compound,ortho-chlor-para-tertiary-amyl-phenol-ortho-carboxylic acid.

'7. A compound having the formula 01- C 0 OZ CHs-C-CH! (3H, C IH;

in which Z is a member of the class consisting of in which CeHu-n is abenzene nucleus, COOZ is 10 a radical in which Z is a member of theclass consisting of hydrogen, an alkali-metal, an alkalineearth-metal,ammonium, and a lower aliphatic amine, X is a halogen, Y is asubstituent radical which is one of the group consisting of the alkyl,aralkyl, aryl, alkoxy, and cycloalkyl radicals, n is an integer notgreater than three, and the total number of carbon atoms in thesubstituent groups in (Y)n is not less than three nor more than twelveper molecule.

GEORGE L. DOELLING.

